1. Technical Field
This document relates to systems and methods for producing biologic tissue. For example, this document relates to using electrospinning systems and culturing techniques to make biologic heart valve leaflets having multiple nanofibrous substrate layers.
2. Background Information
Cardiac valves control blood flow within the heart by opening and closing their leaflets to create and release pressure differentials. Leaflets are primarily composed of valvular interstitial cells (VICs) residing in three apposed layers—a circumferentially oriented fibrosa layer, a randomly oriented spongiosa layer, and a radially oriented ventricularis layer. Collagen, collagen/proteoglycan, and collagen/elastin are the predominant extracellular matrix components in these layers, respectively. A diseased or damaged leaflet may result in valvular regurgitation and/or stenosis that detrimentally affects blood flow through the heart. In some cases, such leaflet dysfunctionalities are triggered by adverse biochemical factors and mechanical stresses on the VICs.
In a healthy heart valve leaflet, VICs show quiescent fibroblast phenotype; however, their pathogenic myofibroblast phenotype is observed in its diseased counterpart. During fetal leaflet development, and in remodeling of fully-grown leaflets, VICs show active myofibroblast phenotype. Further, they show fibroblast phenotype on a soft substrate and active myofibroblast phenotypes on a substrate with high mechanical properties. Active myofibroblasts may cause contractility and in the presence of adverse environment, they may be transformed to pathogenic, which is not desirable.